Lhermitte-Duclos Research Articles

Teaching NeuroImage: Tigroid Appearance of Cerebellum on MRI in Lhermitte-Duclos Disease.

Teaching NeuroImage: Tigroid Appearance of Cerebellum on MRI in Lhermitte-Duclos Disease.

Pathologists' integration of prior biopsies of women with germline PTEN mutations may expedite the identification of this rare cancer predisposition syndrome

PTEN hamartoma tumour syndrome (PHTS) is a rare cancer predisposition syndrome, caused chiefly by pathogenic and likely pathogenic (P/LP) variants in in the PTEN gene. Carriers have substantially elevated risks of various malignancies and develop benign lesions in multiple organ systems. The rarity of this disease, the decades long unfolding of its clinical features, involvement of multiple sites and the absence of distinguishing features of each lesion hamper the identification of this condition, limiting opportunities for screening of affected individuals and their families. Given laboratory information systems are the repositories of patients' biopsies, we are interested in whether PHTS patients' prior biopsies may serve as clues to the possibility of this syndrome. With ethics committee approval, through a collaboration amongst our state-wide Adult Genetics Unit and all pathology laboratories in our state, we have undertaken a 28-year longitudinal survey (1990–2018) of the biopsy histories of 12 women known to have P/LP PTEN variants. Only one woman had a family history of Cowden syndrome, with the remaining 11 patients' mutations becoming discovered later. The earliest biopsy was at age 19. The most common finding was the development of multiple benign mucocutaneous lesions, with 10 women presenting with these. These included a range of benign vascular lesions: eight patients, various fibromatous lesions of the skin and mucosal sites: six patients, a ganglioneuroma and a juvenile polyp. Ten women developed breast cancer, only four before the age of 40. Seven women developed a second breast cancer, two synchronously and five at intervals of 3–11 years. Other neoplasms included endometrial carcinoma (two patients) and dysplastic cerebellar gangliocytoma (three patients). Integrating the biopsy histories of PTEN P/LP variant carriers over time may assist in raising the possibility of an underlying cancer susceptibility syndrome, so appropriate clinical and genetic counselling and evaluation may be considered.

Acute acquired comitant esotropia associated with Lhermitte–Duclos disease: a case report

BackgroundAcute acquired comitant esotropia caused by prolonged near work, such as the use of digital devices, has been frequently reported in recent years. However, intracranial examination is necessary even for patients with nonparalytic comitant esotropia. Lhermitte–Duclos disease is a rare tumor that grows in layers in the cerebellum. Among those with this disease, cases of esotropia have been reported due to abduction limitation of the eye, but there have been no reports of comitant esotropia. Here, we report the case of a young woman with acute acquired comitant esotropia who was found to have Lhermitte–Duclos disease.Case presentationA 16-year-old Japanese female patient, whose ethnicity was Asian, was referred to our hospital for acute acquired comitant esotropia. Fundus examination revealed papilledema in both eyes, and magnetic resonance imaging of the head revealed a cerebellar tumor in the right cerebellum with obstructive hydrocephalus. She underwent partial tumor resection, and a histopathological diagnosis of Lhermitte–Duclos disease was obtained. However, comitant esotropia status remained unchanged, and she underwent strabismus surgery. Finally, diplopia disappeared completely.ConclusionNeurological and intracranial imaging examinations are essential when acute acquired comitant esotropia is observed. Acute acquired comitant esotropia by Lhermitte–Duclos disease did not improve with partial tumor resection and required strabismus surgery, but good surgical results were obtained.

Anomalies of Midbrain Hindbrain Development: Midbrain Clefts, Cerebellar Nodular Heterotopia with Overlying Dysgenesis, Cerebellar Foliation Disorder, Pontine Tegmental Cap Dysplasia; Joubert Syndrome; Lhermitte Duclos Syndrome. Diagnosis, Classification and Rehabilitation Hypothesis

AbstractMidbrain and hindbrain (MBHB) malformations are a rare group of congenital abnormalities that involve the neural structure of the posterior cranial fossa, leading to significant causes of neurodevelopmental dysfunction. Recent advancements in genetic and neuroimaging technologies have significantly enhanced our understanding of these disorders. The integration of these advances has facilitated a systematic classification of these conditions. A basic understanding of MBHB embryology is fundamental in order to understand the malformations occurring in their structures: MBHB neurons are mainly generated in the neuroepithelium, lining the walls of the fourth ventricle. Moreover, the regional specificity of the neural tube is determined by a combination of transcription factors expressed, organizing the fate of the neighboring regions as well. Clinical features of MBHB malformations are typically nonspecific; some patients may be asymptomatic or may develop neurological symptoms including hypotonia, ataxia, abnormal eye movements, decreased visual attention, cranial nerve deficits, cognitive impairment, and psychiatric symptoms. Many malformations have been described. We proposed the description of some of them, reporting their main morphologic aspects, magnetic resonance imaging (MRI) peculiar signs and their clinical presentation. Midbrain clefts, for example, are malformations characterized by median separation in the ventral midbrain which involves a communication with the cerebral aqueduct giving a “keyhole” shape. Pontine tegmental cap dysplasia, instead, is a rare hindbrain malformation responsible for a nonprogressive neurological disorder and is described with hypoplastic flat ventral pons, hypoplasia of the middle cerebellar peduncles, and hypoplasia and malformation of the worm. Joubert syndrome, cerebellar nodular heterotopia, abnormal cerebellar foliation, and Lhermitte–Duclos disease, also called dysplastic cerebellar gangliocytoma, have been described as well in order to provide a general overview on this diagnostic challenge reporting the most recent findings.

A rare case of dysplastic cerebellar gangliocytoma - Lhermitte Duclos Disease

Lhermitte–Duclos disease (LDD), also known as dysplastic cerebellar gangliocytoma, is an uncommon hamartomatous lesion found in the cerebellar cortex. First described by French physicians Lhermitte and Duclos in 1920, this condition involves enlarged cerebellar folia containing abnormal ganglion cells. Clinical manifestations typically include headaches, visual disturbances, and cerebellar dysfunction. While imaging techniques like computed tomography (CT) scans may indicate the presence of mass lesions, magnetic resonance imaging (MRI) is crucial for accurate delineation of the lesion's boundaries and characterization of tissue involvement. Surgical intervention, typically in the form of respective surgery, remains the cornerstone of treatment for LDD. Despite advancements in imaging technologies and surgical techniques, the management of LDD remains fraught with complexities. The prognosis can be variable, and in some cases, despite appropriate therapeutic interventions guided by MRI-assisted surgical planning and confirmation through CT screening, the outcome may be unfavorable, as observed in this instance with the demise of the 50-year-old male patient. Further research and a deeper understanding of the pathophysiology underlying LDD are imperative to enhance diagnostic accuracy, refine treatment modalities, and potentially improve patient outcomes. This case underscores the challenges in managing this rare neurological condition and highlights the need for continued exploration into more effective therapeutic avenues.

Cerebellar phenotypes in germline PTEN mutation carriers.

PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer. Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte-Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations. The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations. In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.

Lhermitte-Duclos disease: A systematic review.

Lhermitte-Duclos disease (LDD) is a rare tumor, with only about 300 reported cases. It often shows comorbidity with Cowden syndrome (CS); however, it can occur by itself. Radiologically, the "tiger-stripe" appearance is considered pathognomonic. Surgical resection remains the mainstay of treatment. This report aims to describe the clinical and radiological characteristics of LDD and its relationship with CS according to age group. PubMed electronic databases were searched in August 2022. The search terms included "Lhermitte- Duclos disease" and "dysplastic gangliocytoma," which yielded 297 and 103 research articles, respectively. The articles were collected and reviewed by three researchers. Out of 400 identified articles, we analyzed 302 reported cases. The mean age at presentation was 33.6 ± 16 years; 171 patients (56.6%) were female, and 123 (40.7%) were male. The most commonly reported symptom was headache (174 patients, 57.6%), followed by ataxia (109, 36.1%). In addition, 99 cases (32.8%) were associated with CS, and 60 (19.9%) had a confirmed phosphatase and tensin homolog (PTEN) mutation. A tiger-stripe appearance was observed in 208 cases (58.7%); surgical resection was performed in 64.2% of the cases. Mortality and recurrence rates were 4.3% and 8.6%, respectively. No statistically significant difference was found between adult- and pediatric-onset LDD for the association with CS (P = 0.128). Our findings suggest that adult and pediatric LDD have major commonalities; however, further prospective studies are warranted.

Pathomorphological Features of Lhermitte-Duclos Disease: A Rare Clinical Observation and Literature Review

Dysplastic Cerebellar Gangliocytoma (DCG) or Lhermitte-Duclos Disease (LDD) is a rare neoplasm in the cerebellum of unclear etiology.

A young Female of Cowden Syndrome Presenting with Lhermitte- Duclos Disease: A Case Study

Cowden Syndrome (CS) is a rare autosomal dominant inherited genetic disorder due to germline mutations in the phosphatase and tensing homologue (PTEN) tumor suppressor gene in chromosome 10 characterized by multiple hamartomata’s lesions of ectodermal, mesodermal and endodermal origin. Lhermitte-Duclos Disease (LDD), or dysplastic gangliocytoma, which is a benign hamartomata’s condition involving the cerebellum with less than 300 cases reported in the literature. Previous studies suggest an association between CS and LDD. We present here a case of a 28-year female patient presented at the emergency department of our hospital with severe headache associated with vertigo, vomiting & cerebellar ataxia. Papilledema was noted on fundoscopy. Non-attenuating hypodense mass lesion in posterior fossa was found in CT scan. MRI scan T1WI film revealed mixed intensity posterior fossa lesion and T2WI film revealed inhomogeneous hyperintense lesion with almost preserved cerebellar cortical striations. USG revealed numerous polyps in the gallbladder with cholelithiasis. Her facial skin has extensive trichilemmoma. Her symptoms improved after excision of posterior fossa lesion through suboccipital craniectomy and histopathology revealed dysplastic cerebellar gangliocytoma i.e., Lhermitte-Duclos disease. Using the Cleveland Clinic Adult Clinical Scoring for PTEN Testing, the patient had an 82-98% chance for a PTEN gene mutation. Finally, she along with her family was adequately counseled and was advised for regular screening and monitoring. Bang. J Neurosurgery 2022; 12(1): 41-46

Lhermitte-Duclos Disease Presenting as Cognitive Impairment: A Case Report with 7 Year Follow-up

Lhermitte-Duclos Disease Presenting as Cognitive Impairment: A Case Report with 7 Year Follow-up

“Leopard skin” sign: Magnetic resonance imaging appearance of Lhermitte-Duclos disease with histopathologic correlation

Dysplastic cerebellar gangliocytoma or Lhermitte-Duclos disease (LDD) is a rare hamartomatous malformation of cerebellum that can occur in isolation or as a component of Cowden syndrome. Although uncommon, the characteristic clinical symptoms and magnetic resonance imaging (MRI) features are highly suggestive of the condition and histopathological features confirm the diagnosis. We report a case of LDD, presenting with “Leopard skin” appearance of the lesion on MRI with a brief review of imaging, clinical, and histopathological features.

Diagnosis of PTEN mosaicism: the relevance of additional tumor DNA sequencing. A case report and review of the literature

BackgroundPTEN hamartoma syndrome (PHTS) is an autosomal dominant disorder characterized by pathogenic variants in the tumor suppressor gene phosphatase and tensin homolog (PTEN). It is associated with an increased risk of muco-cutaneous features, hamartomatous tumors, and cancers. Mosaicism has been found in a few cases of patients with de novo PHTS, identified from blood samples. We report a PHTS patient with no variant identified from blood sample. Constitutional PTEN mosaicism was detected through sequencing of DNA from different tumoral and non-tumoral samples.Case presentationOur patient presented clinical Cowden syndrome at 56 years of age, with three major criteria (macrocephaly, Lhermitte Duclos disease, oral papillomatosis), and two minor criteria (structural thyroid lesions, esophageal glycogenic acanthosis). Deep sequencing of PTEN of blood leukocytes did not reveal any pathogenic variants. Exploration of tumoral (colonic ganglioneuroma, esophageal papilloma, diapneusia fibroids) and non-tumoral stomach tissues found the same PTEN pathogenic variant (NM_000314.4 c.389G > A; p.(Arg130Gln)), with an allelic frequency of 12 to 59%, confirming genomic mosaicism for Cowden syndrome.ConclusionsThis case report, and review of the literature, suggests that systematic tumor analysis is essential for patients presenting PTEN hamartoma syndrome in the absence of any causal variant identified in blood leukocytes, despite deep sequencing. In 65 to 70% of cases of clinical Cowden syndrome, no pathogenic variant in the PTEN is observed in blood samples: mosaicism may explain a significant number of these patients. Tumor analysis would improve our knowledge of the frequency of de novo variations in this syndrome. Finally, patients with mosaicism for PTEN may not have a mild phenotype; medical care identical to that of heterozygous carriers should be offered.

Pathologists’ overview of prior biopsies of women with germline PTEN mutations may expedite the identification of this rare cancer predisposition syndrome

PTEN hamartoma tumour syndrome (PHTS) is a rare cancer predisposition syndrome, caused chiefly by pathogenic and likely pathogenic (P/LP) variants in the PTEN gene. The rarity of this disease, involvement of multiple sites and the absence of pathognomonic features hamper early diagnosis, limiting opportunities for cancer screening. We wondered whether PHTS patients’ prior biopsies may provide clues to this syndrome. With ethics approval, through a collaboration with our state-wide Adult Genetics Unit, we undertook a 28-year survey (1990–2018) of prior biopsies of 12 women known to have P/LP PTEN variants. One woman had a family history of PHTS. The earliest biopsy was at age 19. Multiple benign mucocutanous lesions affected 10 women, including benign vascular lesions: eight patients, fibromatous skin and mucosal lesions: six patients, one ganglioneuroma and one juvenile polyp. Ten women developed breast cancer, four under 40 years. Five women developed a second breast cancer, two synchronously and three at interval of 3–11 years. Other neoplasms included endometrial carcinoma two patients and dysplastic cerebellar gangliocytoma three patients. Overview of the biopsy histories of PTEN P/LP variant carriers may be a clue to the diagnosis, so clinical and genetic counselling and evaluation may be considered.

L’hermitte–Duclos Disease In An Infant: A Case Report With Review of Literature

Jacques Jean Lhermitte a French neurologist and P. Duclos in 1920 first described a growth in the cerebellum gangliocytoma, as a rare hamartomata’s lesion due to abnormal development of the cerebellum. Since then it has been called by many names Lhermitte-Duclos disease, dysplastic gangliocytoma of the cerebellum, benign hypertrophy of the cerebellar cortex, granular cell hypertrophy and Purkinjeoma. It is a characteristic radiological feature and there has been reported in over 200 cases worldwide in adolescents [1] and old people but a handful of cases are detected and reported in infants. We report a 6 month old male child whose parents reported a history of irritability and typical lion facies with normal mile stones and radiological features of L’hermitte–Duclos disease.

Lhermitte-Duclos Disease.

HomeRadiologyVol. 307, No. 1 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyLhermitte-Duclos DiseaseDhairya A. Lakhani , SoHyun BooDhairya A. Lakhani , SoHyun BooAuthor AffiliationsFrom the Department of Radiology, West Virginia University, Ruby Memorial Hospital, 1 Medical Center Dr, Morgantown, WV 26506 (D.A.L., S.H.B.); and Department of Neuroradiology, Rockefeller Neuroscience Institute, West Virginia University, Morgantown, WV (S.H.B.).Address correspondence to D.A.L. (email: [email protected]).Dhairya A. Lakhani SoHyun BooPublished Online:Dec 13 2022https://doi.org/10.1148/radiol.221979MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In An 18-year-old woman with no past medical history presented with chronic headache and new onset cerebellar ataxia. MRI of the brain (Figure, A–D) demonstrated a mass in the left cerebellar hemisphere. The mass was predominantly hyperintense with T2-weighted images with intrinsic hyper- to isointense striations relative to gray matter (Figure, A–B). The mass was predominantly hypointense with T1-weighted images with striations hypo- to isointense relative to gray matter (Figure, C). The mass showed no enhancement with contrast-enhanced images (Figure, D) and did not restrict diffusion with diffusion-weighted images (not shown). Mild obstructive-pattern hydrocephalus was present from compression of the fourth ventricle.Images in an 18-year-old woman who presented with chronic headache and cerebellar ataxia. (A, B) Axial T2-weighted, (C) precontrast T1-weighted, and (D) postcontrast T1-weighted MRI scans of the brain demonstrate a mass in the left cerebellar hemisphere. The mass was predominantly hyperintense with (A, B) T2-weighted images with intrinsic hyper- to isointense striations relative to gray matter and predominantly hypointense with (C) T1-weighted images with hypo- to isointense striations relative to gray matter. No intrinsic contrast enhancement was seen with (D) postcontrast images.Download as PowerPointOpen in Image Viewer The typical striated, corduroy, or tiger-striped folial pattern consisting of alternating bands with T2-weighted and T1-weighted images is characteristic of Lhermitte-Duclos disease or dysplastic cerebellar gangliocytoma, a rare hamartomatous disorder (1,2). It is an Aunt Minnie diagnosis and has close association with Cowden syndrome. Clinically, patients may be asymptomatic or present from symptoms related to mass effect (1).Disclosures of conflicts of interest: D.A.L. RSNA William W. Olmsted Trainee Editorial Fellow (2022). S.H.B. No relevant relationships.

Redefining a Rare CNS Tumour Through Targeted Genetic Sequencing

Abstract AIMS Isolated cerebellar vermis lesions in adults is a rare location and entity with few literature case reports detailing gangliogliomas and gangliocytomas. Using targeted genetic sequencing, traditional histological diagnosis can be refined further, with a clear impact on prognosis as well as possible genetic counselling implications. METHOD A single case of cerebellar vermis lesion, identified incidentally through imaging of a neck nodule, with subtle features of ataxia and mild impairment of initiation of speech. Sub-total resection of lesion underwent standard histopathological work-up, followed by targeted genetic sequencing to obtain an integrated diagnosis. RESULTS Histological assessment identified atypical ganglion cells labelled with Synaptophysin on immunohistochemistry. Features closely resembled dysplastic cerebellar gangliocytoma (Lhermitte-Duclos Disease). Further targeted sequencing showed no evidence of IDH1, IDH2, TERT promoter, or histone mutation, however, BRAF mutation was present, supporting an alternate diagnosis of ganglioglioma. CONCLUSION Precision medicine is facilitated with advanced diagnostic techniques. This redefines categorisation of some CNS tumours, particularly rare entities. Techniques are especially valuable to individual patient management as they can have a direct impact on aspects of clinical work-up, prognosis, follow-up, and in some cases, genetic counselling.

Diverse imaging findings of Lhermitte–Duclos disease

To evaluate the diverse clinical and imaging features of Lhermitte-Duclos disease (LDD) and its subgroup comparison. Clinical data from 21 patients with LDD were collected, including eight patients with LDD without other tumours and 13 LDD with other tumours. Redefined diagnostic criteria are used to evaluate Cowden Syndrome. Imaging indicators were analysed retrospectively to extract typical and atypical features. Imaging findings and preoperative diagnostic accuracy were compared between the subgroups. None of these patients met the redefined diagnostic criteria. The typical "tiger stripe sign" was seen in most LDD lesions (13/29, 61.9%), with lower density (29.66±2.51 versus 37.81±2.76 HU, p<0.001) and higher apparent diffusion coefficient (ADC) value (1.04±0.05×10-3 versus 0.74±0.03×10-3 mm2/s, p<0.001) than that of the normal cerebellum. Atypically, some lesions showed abnormal vessels (8/21, 38.1%), intratumoural calcification (3/21, 14.29%), intratumoural haemorrhage (4/21, 19.05%), peritumoural oedema (6/21, 28.57%), and heterogeneous enhancement (5/21, 23.81%). The typical "tiger stripe sign" was more common in LDD with other tumours (84.62% versus 25%, p=0.018). Although LDD without other tumours was more common with abnormal vessels (75% versus 15.38%, p=0.018), intratumoural calcification (37.5% versus 0, p=0.042), intratumoural haemorrhage (50% versus 0, p=0.012), peritumoural oedema (62.5% versus 7.69%, p=0.014) and heterogeneous enhancement (50% versus 7.69%, p=0.047). Preoperative diagnostic accuracy was higher in LDD with other tumours than LDD without other tumours (76.92% versus 25%, p=0.032). The "tiger stripe sign" of LDD is characteristic, but not unique. With or without other tumours, it may be associated with the imaging diversity. Combining typical and atypical signs can improve the imaging assessment of LDD.

Lhermitte-Duclos Disease Related With Cowden Syndrome Mimicking Metastatic Lung Cancer on FDG PET/CT.

Cowden syndrome is characterized by multiple hamartomatous and neoplastic lesions including Lhermitte-Duclos disease, which is the main criterion for the diagnosis. Herein, we presented a patient with suspected metastatic disease referred to PET/CT, which showed mildly hypermetabolic multinodular thyroid goiter, multiple hamartomatous pulmonary, and breast nodules. Also, intense hypermetabolism was noted on the cerebellar tumor lesion. Lhermitte-Duclos disease was diagnosed based on the characteristic MRI findings, and she was followed up with a diagnosis of Cowden syndrome. Our case indicates that Cowden syndrome should be included as a differential diagnosis of abnormal FDG uptake in the multiple systemic hamartomatous tumors.

Paresthesias and Weakness of Lower Limbs as Symptomatic Debut of Lhermitte-Duclos Disease.

An abstract is not available for this content so a preview has been provided. Please use the Get access link above for information on how to access this content.

Medulloblastoma and Cowden syndrome: Further evidence of an association.

Cowden syndrome (CS) is an autosomal dominant hamartoma and tumor predisposition syndrome caused by heterozygous pathogenic germline variants in PTEN in most affected individuals. Major features include macrocrania, multiple facial tricholemmomas, acral and oral keratoses and papillomas, as well as mammary, non-medullary thyroid, renal, and endometrial carcinomas. Lhermitte-Duclos disease (LDD), or dysplastic gangliocytoma of the cerebellum, is the typical brain tumor associated with CS; the lifetime risk for LDD in CS patients has been estimated to be as high as 30%. In contrast, medulloblastoma is much rarer in CS, with only 4 reported cases in the literature. We report a 5th such patient. All 5 patients were diagnosed between 1 and 2 years of age and not all showed the pathognomonic clinical stigmata of CS at the time of their medulloblastoma diagnosis. Where detailed information was available, the medulloblastoma was of the SHH-subtype, in keeping with the observation that in sporadic medulloblastomas, PTEN-alterations are usually encountered in the SHH-subtype. Medulloblastomas can be associated with several tumor-predisposition syndromes and of the 4 medulloblastoma subtypes, SHH-medulloblastomas in children have the highest prevalence of predisposing germline variants (approx. 40%). CS should be added to the list of SHH-medulloblastoma-associated syndromes. Germline analysis of PTEN should be performed in infants with SHH-medulloblastomas, regardless of their clinical phenotype, especially if they do not carry pathogenic germline variants in PTEN or PTEN, the most commonly altered predisposing genes in this age-group. In addition, these cases show that CS has a biphasic brain tumor distribution, both in regards to the age of onset and the tumor type: a small number of CS patients develop a medulloblastoma in infancy while many more develop LDD in adulthood.